α-Aryloxybenzyl analogues of morpholine are a significant class of compounds because of their influence on the central nervous system (CNS), with particular concentration on their antidepressant potency. (±)-Reboxetine, an example of such α-aryloxybenzyl analogues, is an orally active and selective noradrenaline reuptake inhibitor that is presently recognized as a prescription drug in over 60 countries for depressive sickness and has been spaciously studied for its pharmacological characteristics. (+)-(S,S)-Reboxetine is presently undergoing advanced clinical evaluation as a potential treatment for neuropathic and fibromyalgia pain. Scheming well-organized approaches to access reboxetine and its derivatives represents a significant endeavor not only for developing antidepressant drugs but also advancing medical studies by radiolabeling of reboxetine derivatives with ¹¹C, ¹⁸F, or ¹²³I as potential positron emission tomography radioligands for imaging the brain norepinephrine transporter system. Therefore, to fulfill the challenge of creating the reboxetine architecture by improved synthetic routes, the review combines all of the literature synthetic processes for reboxetine and its derivatives on one platform. Cons and pros of each synthetic method are discussed in this review, which will be very fruitful for the synthetic and medical communities to increase the diversity of synthetic procedures and to develop new concepts and perceptions.

中文翻译：

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重磅炸弹药物的合成故事：瑞波西汀，一种有效的选择性去甲肾上腺素再摄取抑制剂

吗啉的α-芳氧基苄基类似物是一类重要的化合物，因为它们会影响中枢神经系统（CNS），特别是其抗抑郁药的浓度。（±）-瑞波西汀是此类α-芳氧基苄基类似物的一个例子，是一种口服活性和选择性去甲肾上腺素再摄取抑制剂，目前在60多个国家被认为是治疗抑郁症的处方药，并且对其药理特性进行了广泛的研究。（+）-（S，S瑞波西汀目前正在接受先进的临床评估，作为神经性和纤维肌痛疼痛的潜在治疗方法。计划有条理的获取瑞波西汀及其衍生物的方法不仅是开发抗抑郁药的重要举措，而且还通过用¹¹ C，¹⁸ F或¹²³放射性标记瑞波西汀衍生物来推进医学研究。我作为潜在的正电子发射断层扫描放射配体对大脑去甲肾上腺素转运系统进行成像。因此，为了应对通过改进的合成途径创建reboxetine结构的挑战，本综述在一个平台上结合了reboxetine及其衍生物的所有文献合成方法。本综述讨论了每种合成方法的利弊，这对于合成和医学界增加合成程序的多样性并发展新的概念和认识将是非常富有成果的。